2,6-bis(hydroxymethyl)-4-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 1 liter, 3 necked round bottomed flask equipped with a paddle stirrer, condenser, thermometer and heating source, were added 150 g (0.81 mole) of the 2,6-dimethylol-4-methoxyphenol, followed by 9 g (0.1 moles) of oxalic acid and 180 g (1.63 moles) of catechol. To this were added 400 g of water. The reaction mixture was stirred and heated to 70° C. Solution occurred when the temperature reached approximately 60° C. Then, the reaction mixture was heated to reflux and held at reflux for 4 hours. After 1 hour at reflux, the product began to separate. To a 1 liter, 3 necked round bottomed flask equipped with a paddle stirrer, condenser thermometer and heating source reached approximately 60° C Then, the reaction mixture was heated to reflux at reflux for 4 hours After 1 hour at reflux to separate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 1 liter, 3 necked round bottomed flask equipped with a paddle stirrer, condenser, thermometer and heating source, were added 150 g (0.81 mole) of the 2,6-dimethylol-4-methoxyphenol, followed by 9 g (0.1 moles) of oxalic acid and 180 g (1.63 moles) of catechol. To this were added 400 g of water. The reaction mixture was stirred and heated to 70° C. Solution occurred when the temperature reached approximately 60° C. Then, the reaction mixture was heated to reflux and held at reflux for 4 hours. After 1 hour at reflux, the product began to separate. To a 1 liter, 3 necked round bottomed flask equipped with a paddle stirrer, condenser thermometer and heating source reached approximately 60° C Then, the reaction mixture was heated to reflux at reflux for 4 hours After 1 hour at reflux to separate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 30.0 g (174 mmol) 5-chloro-2-nitroaniline (Aldrich), conc. HCl (aq) (J. T. Baker), 100 ml deionized water and 100 ml absolute ethanol. The suspension was cooled to 0° C. and 12.7 g (184 mmol) sodium nitrite in 50 ml water was added dropwise over 30 minutes while keeping the reaction mixture at 0° C. The reaction mixture was stirred for an additional 1 hour. Sulfamic acid (430 mg) was added to destroy excess nitrite and the reaction mixture was stirred for an additional 20 minutes. The solids were filtered and the filtrate containing the diazonium salt was set aside and kept cold at −10° C. NaOH (34.9 g, 873 mmol) was dissolved in 100 ml water and approximately one-fourth was added to a solution of (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol in 100 ml deionized water and 200 ml ethanol. The diazonium salt mixture and remaining sodium hydroxide solution were added to the reaction mixture containing the phenol derivative over a 1 hour period at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and ambient temperature for 2 hours. The contents were poured into 3 liters water and the pH was adjusted to 5 using 1N HCl. The resultant solid was washed with several liters of water and then vacuum dried (0.1 mm Hg) at 55° C. for 40 hours using P2O5 as drying agent to afford 28.0 g (48%) of a dark solid which was used in the next step without further purification. In a 500 ml round bottom flask equipped with a magnetic stirrer at 0° C to destroy excess nitrite the reaction mixture was stirred for an additional 20 minutes The solids were filtered the filtrate containing the diazonium salt kept cold at −10° C were added to the reaction mixture to stir at 0° C. for 1 hour and ambient temperature for 2 hours The resultant solid was washed with several liters of water vacuum dried (0.1 mm Hg) at 55° C. for 40 hours as drying agent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 19.9 g (144 mmol) 2-nitroaniline (Aldrich), HCl (aq), 100 ml deionized water, and 100 ml EtOH. The mixture was cooled to 0° C. and 10.6 g (153 mmol) sodium nitrite in 50 ml water was added dropwise over 60 minutes while keeping the reaction mixture between −10-0° C. The reaction mixture was stirred for an additional 1 hour. 300 mg sulfamic acid was added to destroy excess nitrite and the mixture was stirred for an additional 20 minutes. The solids were filtered and the filtrate containing the diazonium salt was set aside and kept cold at −10° C. NaOH (29.3 g, 731 mmol) was dissolved in 100 ml water and approximately one-fourth was added to a solution of (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol in 100 ml deionized water and 200 ml ethanol. The diazonium salt mixture and remaining sodium hydroxide solution were added to the reaction mixture containing the phenol derivative over a 1 hour period at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and ambient temperature for 3 hours. The contents were poured into 3 liters water and the pH was adjusted to 6 using 1N HCl. The resultant solid was washed with several liters of water and then dried at 55° C. for 40 hours using P2O5 as drying agent to afford 24.4 g (55.8%) of a dark solid which was used in the next step without further purification. In a 500 ml round bottom flask equipped with a magnetic stirrer between −10-0° C to destroy excess nitrite the mixture was stirred for an additional 20 minutes The solids were filtered the filtrate containing the diazonium salt kept cold at −10° C were added to the reaction mixture to stir at 0° C. for 1 hour and ambient temperature for 3 hours The resultant solid was washed with several liters of water dried at 55° C. for 40 hours as drying agent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 25.1 g (161 mmol) 4-fluoro-2-nitroaniline (Aldrich), HCl (aq) (J. T. Baker), 100 ml deionized water, and 100 ml absolute ethanol. The suspension was cooled to 0° C. 11.8 g (171 mmol) Sodium nitrite (Sigma-Aldrich) in 50 ml water was added dropwise over 60 minutes while keeping the reaction mixture at 0° C. The reaction mixture was stirred for an additional 1 hour. 420 mg sulfamic acid (Aldrich) was added and the reaction mixture was stirred for an additional 30 minutes and then filtered. In a 1 liter round bottom flask was combined 32.5 g (176 mmol) (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol, 200 ml deionized water, and 200 ml ethanol. 32.3 g (807 mmol) NaOH (Aldrich) was dissolved in 100 ml water and approximately one-fourth of this was added to the solution containing the phenol derivative at 0° C. The diazonium salt solution and remaining sodium hydroxide solution were added dropwise to the reaction mixture at 0° C. over a 1 hour period and then allowed to stir for an additional 1 hour at 0° C. and 3 hours at ambient temperature. The reaction mixture was poured into 3 liters water and the pH was adjusted to 4 using 1N HCl. The solid was collected by filtration, washed with several liters of water, and vacuum dried (0.1 mm Hg) at 55° C. for 72 hours using P2O5 as drying agent to afford 29.9 g (68%) of a dark solid which was used in the next step without further purification. In a 500 ml round bottom flask equipped with a magnetic stirrer at 0° C the reaction mixture was stirred for an additional 30 minutes filtered In a 1 liter round bottom flask was combined approximately one-fourth of this was added to the solution were added dropwise to the reaction mixture at 0° C. over a 1 hour period to stir for an additional 1 hour at 0° C. and 3 hours at ambient temperature The solid was collected by filtration washed with several liters of water, and vacuum dried (0.1 mm Hg) at 55° C. for 72 hours as drying agent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 19.9 g 2-nitro-4-(trifluoromethyl)-aniline (96.5 mmol) (Aldrich, Milwaukee, Wis.), 41 ml concentrated HCl (aq), 100 ml deionized water, 100 ml ethanol, and 80 ml THF. The suspension was stirred for 30 minutes and 7.07 g sodium nitrite (102 mmol) in 30 ml water was added dropwise over 60 minutes while keeping the reaction mixture at 0° C. The reaction mixture was stirred for an additional 1 hour. 300 mg Sulfamic acid was added to destroy excess nitrite. The mixture was filtered to remove undissolved solids. The filtered diazonium mixture along with a solution of sodium hydroxide (15.1 g in 100 ml water) were added dropwise to a solution containing 19.7 g (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol (107 mmol), 4.3 sodium hydroxide, 200 ml deionized water, and 50 ml THF at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and room temperature for 4 hours. The mixture was poured into 3 liters water. The mixture was acidified to pH 3-4. The dark crude product was filtered and washed with several liters of water to generate a dark solid which was dried under high vacuum at 55° C. for 72 hours to give 15.2 g (42% yield) product. In a 500 ml round bottom flask equipped with a magnetic stirrer at 0° C The reaction mixture was stirred for an additional 1 hour to destroy excess nitrite The mixture was filtered to remove undissolved solids The filtered diazonium mixture along with a solution of sodium hydroxide (15.1 g in 100 ml water) were added dropwise to a solution at 0° C to stir at 0° C. for 1 hour and room temperature for 4 hours The dark crude product was filtered washed with several liters of water was dried under high vacuum at 55° C. for 72 hours

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 24.8 g (148 mmol) 4-methoxy-2-nitroaniline (Aldrich), conc. HCl(aq) (J.T. Baker), 150 ml water, and 150 ml absolute ethanol. The mixture was cooled to −20° C. and a solution comprised of 10.8 (156 mmol) sodium nitrite in 40 ml water was added dropwise over 30 minutes. The reaction mixture was stirred for an additional 1 hour and then sulfamic acid (315 mg) was added to destroy excess nitrite. The undissolved solids were filtered and the filtrate containing the diazonium salt was set aside and kept cold at −10° C. NaOH (29.5 g, 739 mmol) was dissolved in 100 ml water and approximately one-fourth was added to a solution comprised of (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol in 100 ml deionized water and 200 ml ethanol. The diazonium salt mixture and remaining sodium hydroxide solution were added to the reaction mixture containing the phenol derivative over a 1 hour period at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and ambient temperature for 3 hours. The contents were poured into 3 liters water and the pH was adjusted to 4.5 using 1N HCl. The resultant solid was filtered, washed with several liters of water, and then vacuum dried (0.1 mm Hg) at 65° C. for 20 hours using P2O5 as drying agent to afford 33.5 g (68%) of a dark solid which was used in the next step without further purification. In a 500 ml round bottom flask equipped with a magnetic stirrer was added dropwise over 30 minutes to destroy excess nitrite The undissolved solids were filtered the filtrate containing the diazonium salt kept cold at −10° C approximately one-fourth was added to a solution were added to the reaction mixture to stir at 0° C. for 1 hour and ambient temperature for 3 hours The resultant solid was filtered washed with several liters of water vacuum dried (0.1 mm Hg) at 65° C. for 20 hours as drying agent

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml round bottom flask equipped with a magnetic stirrer was added 30.0 g (174 mmol) 5-chloro-2-nitroaniline (Aldrich), conc. HCl(aq) (J.T. Baker), 100 ml deionized water and 100 ml absolute ethanol. The suspension was cooled to 0° C. and 12.7 g (184 mmol) sodium nitrite in 50 ml water was added, dropwise over 30 minutes while keeping the reaction mixture at 0° C. The reaction mixture was stirred for an additional 1 hour. Sulfamic acid (430 mg) was added to destroy excess nitrite and the reaction mixture was stirred for an additional 20 minutes. The solids were filtered and the filtrate containing the diazonium salt was set aside and kept cold at −10° C. NaOH (34.9 g, 873 mmol) was dissolved in 100 ml water and approximately one-fourth was added to a solution of (2-hydroxy-5-methoxy-1,3-phenylene)dimethanol in 100 ml deionized water and 200 ml ethanol. The diazonium salt mixture and remaining sodium hydroxide solution were added to the reaction mixture containing the phenol derivative over a 1 hour period at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and ambient temperature for 2 hours. The contents were poured into 3 liters water and the pH was adjusted to 5 using 1N HCl. The resultant solid was washed with several liters of water and then vacuum dried (0.1 mm Hg) at 55° C. for 40 hours using P2O5 as drying agent to afford 28.0 g (48%) of a dark solid which was used in the next step without further purification. In a 500 ml round bottom flask equipped with a magnetic stirrer at 0° C to destroy excess nitrite the reaction mixture was stirred for an additional 20 minutes The solids were filtered the filtrate containing the diazonium salt kept cold at −10° C were added to the reaction mixture to stir at 0° C. for 1 hour and ambient temperature for 2 hours The resultant solid was washed with several liters of water vacuum dried (0.1 mm Hg) at 55° C. for 40 hours as drying agent